Sensor for transcutaneous measurement of vascular access blood flow

ABSTRACT

An optical sensor includes photoemitter and photodetector elements at multiple spacings (d 1 , d 2 ) for the purpose of measuring the bulk absorptivity (α) of an area immediately surrounding and including a hemodialysis access site, and the absorptivity (α o ) of the tissue itself. At least one photoemitter element and at least one photodetector element are provided, the total number of photoemitter and photodetector elements being at least three. The photoemitter and photodetector elements are collinear and alternatingly arranged, thereby allowing the direct transcutaneous determination of vascular access blood flow.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present patent application is a continuation-in-part ofapplication Ser. No. 09/084,958, filed May 28, 1998, which is acontinuation of application Ser. No. 08/479,352, filed Jun. 7, 1995 (nowU.S. Pat. No. 5,803,908), which is a continuation of application Ser.No. 08/317,726, filed Oct. 4, 1994 (now U.S. Pat. No. 5,499,627), whichis a divisional of application Ser. No. 08/011,882, filed Feb. 1, 1993(now U.S. Pat. No. 5,372,136), which is a continuation of applicationSer. No. 07/598,169, filed Oct. 16, 1990 (abandoned); and acontinuation-in-part of application Ser. No. 09/244,756, filed Feb. 5,1999, which claims the benefit of Provisional Application No.60/073,784, filed Feb. 5, 1998), all of which are incorporated herein byreference in their entireties.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to apparatus for non-invasivelymeasuring one or more blood parameters. More specifically, the inventionrelates to apparatus for the transcutaneous measurement of vascularaccess blood flow. The invention can also be used for precise accesslocation, as a “flow finder,” and also can be used to locate grafts andto localize veins in normal patients for more efficient canulatization.

[0004] 2. Related Art

[0005] Routine determination of the rate of blood flow within thevascular access site during maintenance hemodialysis is currentlyconsidered an integral component of vascular access assessment. Whilethe relative importance of vascular access flow rates and venouspressure measurements in detecting venous stenoses is still somewhatcontroversial, both the magnitude and the rate of decrease in vascularaccess flow rate have been previously shown to predict venous stenosesand access site failure. The traditional approach for determining thevascular access flow rate is by Doppler flow imaging; however, theseprocedures are expensive and cannot be performed during routinehemodialysis, and the results from this approach are dependent on themachine and operator.

[0006] Determination of the vascular access flow rate can also beaccurately determined using indicator dilution methods. Early indicatordilution studies determined the vascular access flow rate by injectingcardiogreen or radiolabeled substances at a constant rate into thearterial end of the access site and calculated the vascular access flowrate from the steady state downstream concentration of the injectedsubstance. These early attempts to use indicator dilution methods werelimited to research applications since this approach could not beroutinely performed during clinical hemodialysis. It has long been knownthat in order to determine the vascular access flow (ABF) rate duringthe hemodialysis procedure, the dialysis blood lines can be reversed (byswitching the arterial and venous connections) to direct the blood flowwithin the hemodialysis circuit in order to facilitate the injection ofan indicator in the arterial end of the access site and detect itsconcentration downstream (N. M. Krivitski, “Theory and validation ofaccess flow measurements by dilution technique during hemodialysis,”Kidney Int 48:244-250, 1995; N. M. Krivitski, “Novel method to measureaccess flow during hemodialysis by ultrasound velocity dilutiontechnique,” ASAIO J 41:M741-M745, 1995; and T. A. Depner and N. M.Krivitski, “Clinical measurement of blood flow in hemodialysis accessfistulae and grafts by ultrasound dilution,” ASAIO J 41:M745-M749,1995)). D. Yarar et al., Kidney Int., 65: 1129-1135 (1999), developed asimilar method using change in hematocrit to determine ABF. Variousmodifications of this approach have been subsequently developed. Whilethese latter indicator dilution methods permit determination of thevascular access flow rate during routine hemodialysis, reversal of thedialysis blood lines from their normal configuration is inconvenient andtime-consuming since it requires that the dialyzer blood pump be stoppedand the dialysis procedure is relatively inefficient during theevaluation of the flow rate which can take up to twenty minutes.Furthermore, some of these indicator dilution methods also requireaccurate determination of the blood flow rate.

[0007] Clinical usefulness and ease of use are major developmentalcriteria. From a routine clinical point of view the need to design asimple sensor, easily attached to the patient, requiring no linereversals, no knowledge of the dialysis blood flow rate, Q_(b), andtranscutaneously applied to skin, thereby accomplishing the measurementwithin a total of 1-2 minutes, is crucial to have repeated, routinemeaningful ABF trend information, whereby access health is easilytracked.

SUMMARY OF THE INVENTION

[0008] It is therefore an object of the present invention to provideapparatus for non-invasively measuring one or more blood parameters.

[0009] It is another object of the present invention to provide anoptical hematocrit sensor that can detect changes in hematocrittranscutaneously.

[0010] It is still another object of the invention to provide an opticalhematocrit sensor that can be used to determine the vascular access flowrate within 2 minutes and without reversal of the dialysis blood linesor knowledge of Q_(b), all transcutaneously.

[0011] These and other objects of the invention are achieved by theprovision of an optical sensor including complementary emitter anddetector elements at multiple spacings (d₁, d₂) for the purpose ofmeasuring the bulk absorptivity (α) of the volume immediatelysurrounding and including the access site, and the absorptivity (α_(o))of the tissue itself.

[0012] In one aspect of the invention, the optical sensor systemcomprises an LED of specific wavelength and a complementaryphotodetector. A wavelength of 805 nm-880 nm, which is near the knownisobestic wavelength for hemoglobin, is used.

[0013] When the sensor is placed on the surface of the skin, the LEDilluminates a volume of tissue, and a small fraction of the lightabsorbed and back-scattered by the media is detected by thephotodetector. The illuminated volume as seen by the photodetector canbe visualized as an isointensity ellipsoid, as individual photons oflight are continuously scattered and absorbed by the media. Because awavelength of 805 nm-880 nm is used, hemoglobin of the blood within thetissue volume is the principal absorbing substance. The scattering andabsorbing characteristics are mathematically expressed in terms of abulk attenuation coefficient (a) that is specific to the illuminatedmedia. The amount of light detected by the photodetector is proportionalvia a modified Beer's law formula to the instantaneous net a value ofthe media.

[0014] When the volume of tissue illuminated includes all or even partof the access, the resultant a value includes information about both thesurrounding tissue and the access itself. In order to resolve the signaldue to blood flowing within the access from that due to the surroundingtissues, the sensor system illuminates adjacent tissue regions on eitherside of the access. Values of α_(o) for tissue regions not containingthe access are then used to normalize the signal, thus providing abaseline from which relative changes in access hematocrit can beassessed.

[0015] Other objects, features and advantages of the present inventionwill be apparent to those skilled in the art upon a reading of thisspecification including the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The invention is better understood by reading the followingDetailed Description of the Preferred Embodiments with reference to theaccompanying drawing figures, in which like reference numerals refer tolike elements throughout, and in which:

[0017]FIG. 1 is a diagrammatic view of a dialysis circuit in which aTQ_(a) hematocrit sensor in accordance with the present invention isplaced at the hemodialysis vascular access site.

[0018]FIG. 2 is a perspective view of a first embodiment of a TQ_(a)hematocrit sensor in accordance with the present invention.

[0019]FIG. 3 is a bottom plan view of the TQ_(a) hematocrit sensor ofFIG. 2.

[0020]FIG. 4 is a side elevational view of the TQ_(a) hematocrit sensorof FIG. 2.

[0021]FIG. 5 is a top plan view of the TQ_(a) hematocrit sensor of FIG.2.

[0022]FIG. 6 is a cross-sectional view taken along line 6-6 of FIG. 2.

[0023]FIG. 7 is a diagrammatic view illustrating the TQ_(a) sensor ofFIG. 2 and the illuminated volumes or “glowballs” produced by theemitters and seen by the detectors thereof.

[0024]FIG. 8 is a perspective view of a second embodiment of a TQ_(a)hematocrit sensor in accordance with the present invention.

[0025]FIG. 9 is a bottom plan view of the TQ_(a) hematocrit sensor ofFIG. 8.

[0026]FIG. 10 is a side elevational view of the TQ_(a) hematocrit sensorof FIG. 8.

[0027]FIG. 11 is a top plan view of the TQ_(a) hematocrit sensor of FIG.8.

[0028]FIG. 12 is a cross-sectional view taken along line 12-12 of FIG.9.

[0029]FIG. 13 is a diagrammatic view illustrating the TQ_(a) hematocritsensor of FIG. 8 and the illuminated volumes or “glowballs” produced bythe emitters and seen by the detector thereof.

[0030]FIG. 14 is a perspective view of a third embodiment of a TQ_(a)hematocrit sensor in accordance with the present invention.

[0031]FIG. 15 is a bottom plan view of the TQ_(a) hematocrit sensor ofFIG. 14.

[0032]FIG. 16 is a side elevational view of the TQ_(a) hematocrit sensorof FIG. 14.

[0033]FIG. 17 is a top plan view of the TQ_(a) hematocrit sensor of FIG.14.

[0034]FIG. 18 is a cross-sectional view taken along line 18-18 of FIG.15.

[0035]FIG. 19 is a diagrammatic view illustrating the TQ_(a)-hematocritsensor of FIG. 14 and the illuminated volumes or “glowballs” produced bythe emitter and seen by the detectors thereof.

[0036]FIG. 20 is a perspective view of a fourth embodiment of a TQ_(a)hematocrit sensor in accordance with the present invention.

[0037]FIG. 21 is a partial cross-sectional view of the TQ_(a) hematocritsensor of FIG. 20.

[0038]FIG. 22 is a diagrammatic view of the TQ_(a) hematocrit sensor ofFIG. 20 showing the placement of the emitters and detectors relative tothe access site.

[0039] FIGS. 23-26 are diagrammatic views illustrating the TQ_(a)hematocrit sensor of FIG. 20 and the illuminated volumes or “glowballs”produced by the emitters and seen by the detectors thereof.

[0040]FIG. 27 is a perspective view of a fifth embodiment of a TQ_(a)hematocrit sensor in accordance with the present invention.

[0041]FIG. 28 is a partial cross-sectional view of the TQ_(a) hematocritsensor of FIG. 27.

[0042]FIG. 29 is a diagrammatic view of the TQ_(a) hematocrit sensor ofFIG. 27 showing the placement of the emitters and detectors relative tothe access site.

[0043] FIGS. 30-33 are diagrammatic views illustrating the TQ_(a)hematocrit sensor of FIG. 27 and the illuminated volumes or “glowballs”produced by the emitters and seen by the detectors thereof.

[0044]FIG. 34 is a cross-sectional view of a TQ_(a) hematocrit sensor inaccordance with the present invention in the form of a disposableadhesive patch.

[0045]FIG. 35 is a graphical representation of a signal proportional tothe hematocrit in the vascular access as recorded by a sensor andassociated monitoring system in accordance with the invention.

[0046]FIG. 36 is a graphical representation of plotted values of thevascular access flow rate determined using a TQ_(a) sensor in accordancewith the present invention versus that determined by a conventional HD01monitor.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0047] In describing preferred embodiments of the present inventionillustrated in the drawings, specific terminology is employed for thesake of clarity. However, the invention is not intended to be limited tothe specific terminology so selected, and it is to be understood thateach specific element includes all technical equivalents that operate ina similar manner to accomplish a similar purpose.

[0048] The following abbreviations and variables are used throughout thepresent disclosure in connection with the present invention:

[0049] α=access site optical attenuation coefficient

[0050] α_(o)=non-access site optical attenuation coefficient

[0051] B_(o)=composite of all the non-access region S, K coefficients

[0052] C=proportionality scalar

[0053] CPR=cardiopulmonary recirculation

[0054] d=distance between the emitter and the detector

[0055] H=hematocrit, generally

[0056] H_(a)=hematocrit within the vascular access site

[0057] H_(ao)=hematocrit beneath the sensor (outside the dialyzer)

[0058] ΔH=change in hematocrit (H_(a)−H_(ao))

[0059] i=intensity of light, generally

[0060] I_(baseline)=baseline intensity (taken in the absence of a bolus)

[0061] I_(measure)=light back-scattered from a turbid tissue sample

[0062] I_(o)=emitter radiation intensity

[0063] K=bulk absorption coefficient

[0064] K_(b)=access site blood coefficient

[0065] Q_(a)=vascular access blood flow rate

[0066] Q_(b)=dialyzer blood flow rate

[0067] Q_(f)=dialyzer ultrafiltration rate

[0068] Q_(i)=average injection inflow rate

[0069] S=bulk scattering coefficient

[0070] SD=standard deviation

[0071] SNR=signal-to-noise ratio

[0072] t=time (measured from time of injection)

[0073] TQ_(a)=transcutaneous access blood flow

[0074] V=known volume of saline injected into dialysis venous line

[0075] X_(b)=percentage of the access volume to the total volumeilluminated (access blood proration value)

[0076] X_(o)=percentage of the non-access area to the total volume

[0077] The optical hematocrit sensor in accordance with the presentinvention comprises a light emitting source (emitter) (preferably an LEDof specific wavelength) and a complementary photodetector that can beplaced directly on the skin over a vascular access site. The LEDpreferably emits light at a wavelength of 805 nm-880 nm, because it isnear the known isobestic wavelength for hemoglobin, is commerciallyavailable, and has been shown to be effective in the opticaldetermination of whole blood parameters such as hematocrit and oxygensaturation.

[0078] When the sensor is placed on the surface of the skin, the LEDilluminates a volume of tissue, and a small fraction of the lightabsorbed and back-scattered by the media is detected by thephotodetector. While light travels in a straight line, the illuminatedvolume as seen by the photodetector can be visualized as an isointensityellipsoid, as individual photons of light are continuously scattered andabsorbed by the media. Because a wavelength of 805 nm-880 nm is used,hemoglobin of the blood within the tissue volume is the principalabsorbing substance. The scattering and absorbing characteristics aremathematically expressed in terms of a bulk attenuation coefficient (α)that is specific to the illuminated media. The amount of light detectedby the photodetector is proportional via a modified Beer's law formulato the instantaneous net a value of the media.

[0079] When the volume of tissue illuminated includes all or even partof the access, the resultant α_(o) value includes information about boththe surrounding tissue and the access itself. In order to resolve thesignal due to blood flowing within the access from that due to thesurrounding tissues, the sensor system illuminates adjacent tissueregions on either side of the access. Values of α_(o) for tissue regionsnot containing the access are then used to normalize the signal, thusproviding a baseline from which relative changes can be assessed inaccess hematocrit in the access blood flowing directly under the skin.

[0080]FIG. 1 illustrates a dialysis circuit in which a TQ_(a) hematocritsensor 12 in accordance with the present invention is placed over thehemodialysis vascular access site 14, with the dialysis arterial andvenous blood lines 16 a and 16 b in the normal configuration, formeasuring TQ_(a). A dialyzer 20 downstream of the vascular access site14 and a syringe 22 for injecting a reference diluent (for example,saline) downstream of the dialyzer 20 are indicated. The hematocrits andflow rates under steady state conditions are also indicated, where Q_(a)is the access flow rate, Q_(b) is the dialyzer blood flow rate, Q_(i) isthe injection flow rate, H_(a) is the hematocrit in the access flow, andH_(o) is the hematocrit at the sensor 12. The hematocrit sensor 12 isplaced directly on the skin over the vascular access site 14 downstreamof the venous dialysis needle 24.

[0081] As shown in FIG. 35, the sensor 12 and an associated monitoringsystem 30 records a signal proportional to the hematocrit in thevascular access site 14 (H_(a)). The monitoring system 30 can be acomputer including a computer processor and memory, and output meanssuch as a video monitor and printer (not shown). After a stable Ha valueis obtained, a known volume (V) of normal saline is injected via thesyringe 22 into the dialysis venous line 16 b, which reduces thehematocrit beneath the sensor 12 to a time-dependent hematocrit H_(o)during the injection.

[0082] Derivation of the equation used to calculate the vascular accessflow rate when using the bolus injection indicator dilution approach iscomplex. However, the constant infusion and bolus injection indicatordilution approaches yield identical results; therefore, the governingequation was derived from steady state constant infusion principles.Consider the dialysis circuit in FIG. 1 where a steady infusion ofsaline occurs in the dialysis venous blood line 16 b (ultrafiltration atthe dialyzer 20 is neglected). Red cell balance where the dialysisvenous blood flow enters the access site 14 requires

H _(a)(Q _(a) −Q _(b))+H _(a) Q _(b) =H _(o)(Q _(a) +Q _(i))  (1)

[0083] Solving for Q_(a), the vascular access flow rate, yields$\begin{matrix}{Q_{a} = \frac{Q_{i}}{\frac{\Delta \quad H}{H_{o}}}} & (2)\end{matrix}$

[0084] where ΔH denotes H_(a)−H_(ao). This equation describes thechanges in hematocrit at the sensor 12 during a constant infusion ofnormal saline in the dialysis venous blood line 16 b. (Ifultrafiltration at the dialyzer 20 occurs at a rate of Q_(f), then thenumerator in this equation becomes Q_(i)−Q_(f)).

[0085] Noting that Q_(i) is equivalent to the volume of saline injectedin a specified time interval, equation (2) is therefore equivalent to:$\begin{matrix}{Q_{a} = \frac{V}{\int{{F\left( \frac{\Delta \quad H}{H} \right)}(t){t}}}} & (3)\end{matrix}$

[0086] to yield the vascular access flow rate (Q_(a)), where ΔH denotesH_(a)−H_(ao) and the integral (area under the curve) in the aboveequation is from the time of injection (t=0) to where the signal hasreturned to the baseline value (t=∞). This equation is valid independentof the rate of saline injection or the dialyzer blood flow rate. Thesignals detected by the TQ_(a) sensor 12 can be used to calculate${F\left( \frac{\Delta \quad H}{H_{o}} \right)}.$

[0087] Determination ${fF}\left( \frac{\Delta \quad H}{H} \right)$

[0088] The percentage change in blood parameters (both macroscopic andmicroscopic) passing through the access site 14 may be measured in avariety of ways. Macroscopic parameters such as bulk density or flowenergy can be measured by ultrasonic, temperature, or conductivitymeans. Microscopic parameters (sometimes called “physiologic orintrinsic” parameters) such as hematocrit or red cell oxygen content aremeasured by optical means. Each technique has its respective advantagesand disadvantages, both rely on the quantity$\frac{\Delta \quad H}{H}.$

[0089] Inherent in all of these is the need to differentiate the accesssite 14, and parameter changes therein, from the surrounding tissuestructure. The TQ_(a) sensor 12 in accordance with the present inventionis positioned directly over the access site region 14 itselfapproximately 25 mm downstream of the venous needle 24, and is basedupon optical back-scattering of monochromatic light (λ=805 nm−880 nm)from the blood flow in the access site 14 and the surrounding tissues.The theory on which the construction of the TQ_(a) sensor 12 is basedrequires the use of optical physics and laws associated with opticaldetermination of physiologic elements including hematocrit.

[0090] Modified Beer's Law

[0091] Numerous studies have shown that light back-scattered from aturbid tissue sample follows a modified form of Beer's Law,

I _(measured) =I _(o) Ae ^(−ad)  (4)

[0092] where I_(o) is the radiation intensity emitted from the LED, A isa complex function of d and α of the various layers of tissue(epidermis, dermis, and subcutaneous tissue), d is the distance betweenthe LED and detector, and a is the bulk optical attenuation coefficient.The α term is a function of the absorption and scattering nature of thetissue and has a strong dependence on hematocrit. $\begin{matrix}{\alpha \approx \frac{{- L}\quad n\quad \left( \frac{I_{measured}}{I_{o}} \right)}{d}} & (5)\end{matrix}$

[0093] Compartmentalization of α

[0094] A transcutaneously measured a value is actually a proratedcomposite measure of all the absorption and scattering elementscontained within the illuminated volume or “glowball” of the emittersource, and typically includes the effects of tissue, water, bone,blood, and in the case of hemodialysis patients, the access site 14. Inthe determination of a, clearly only the blood flowing through theaccess site 14 is of interest. The task therefore becomes one ofseparating the effects of absorption and scattering of the access site14 from that of surrounding tissue structure. Starting with the wellknown definition,

α={square root}{square root over (3K(K+S))}  (6)

[0095] where K is the bulk absorption coefficient and S is the bulkscattering coefficient, and separating the access site 14 fromnon-access blood coefficients and rearranging terms,

X _(b) K _(b)≈α² −B _(o)  (7)

[0096] where

[0097] X_(b)=ratio of the access volume to the total volume illuminated

[0098] K_(b)=access blood coefficient

[0099] B_(o)=composite of all the non-access region S and K coefficients

[0100] Now, letting the non-access components become α_(o) ²=B_(o), wehave

X _(b) K _(b) =X _(b) =α ²−α_(o) ²  (8)

[0101] In equation (6), the access blood coefficient, K_(b), is directlyproportional to hematocrit (H), K_(b)=H·C. Therefore,

X _(b) K _(b) =X _(b) ·H·C=α ²−α_(o) ²  (9)

[0102] where C is a proportionality scalar known from the literature orempirically derived.

[0103] To determine α_(o), measurements are made in areas 130 b and 130c near but not including the access site 14, as depicted, for example,in FIG. 7. If the tissue is more or less homogenous, it is onlynecessary to make a single reference α_(o) measurement, using either twoemitters 202 a and 202 b and one detector 204 (as shown in FIG. 13) orone emitter 302 and two detectors 304 a and 304 b (as shown in FIG. 19),as discussed in greater detail hereinafter. On the other hand, if agradient in α_(o) exists in the area of interest (and this is often thecase in vivo) multiple measurements are made to establish the nature ofthe gradient and provide an averaged estimate of α_(o), using twoemitters 102 a and 102 b and two detectors 104 a and 104 b, as discussedin greater detail hereinafter in connection with FIGS. 2-6.

[0104] Determination of $\frac{di}{i}$

[0105] The value of $\frac{di}{i}$

[0106] is defined as the time derivative of intensity i, normalized byi. This is expressed as $\begin{matrix}{{{\frac{di}{i} = {\frac{{X_{b} \cdot \Delta}\quad K_{b}}{\alpha}\left( {d - \frac{1}{\alpha}} \right)}},{{{where}\quad A} \approx \alpha},{{from}\quad {{equation}{\quad \quad}(4)}}}{{or},{{{X_{b} \cdot \Delta}\quad K_{b}} = \frac{\frac{d_{i}}{i}\alpha}{\left( {d - \frac{1}{\alpha}} \right)}}}} & (10)\end{matrix}$

[0107] wherein ΔK_(b) is proportional to ΔH. Hence, $\begin{matrix}{{{X_{b} \cdot \Delta}\quad {H \cdot C}} = {{{X_{b} \cdot \Delta}\quad K_{b}} = \frac{\frac{d_{i}}{i}\alpha}{\left( {d - \frac{1}{\alpha}} \right)}}} & (11)\end{matrix}$

[0108] To determine $\frac{d\quad i}{i},$

[0109] a baseline intensity (taken in the absence of a bolus) is firstmeasured to establish a reference. The intensity is then measured as atime varying signal as the saline bolus is injected, I(t). The quantity$\frac{d\quad i}{i}$

[0110] is then calculated as $\begin{matrix}{\frac{d\quad i}{i} = \frac{I_{baseline} - {I(t)}}{I_{baseline}}} & (12)\end{matrix}$

[0111] Final Determination of$F\left( \frac{\Delta \quad H}{H} \right)$

[0112] The value $F\left( \frac{\Delta \quad H}{H} \right)$

[0113] is the ratio of equations (11) and (8), $\begin{matrix}{{F\left( \frac{\Delta \quad H}{H} \right)} = {\frac{\frac{d\quad i}{i}\alpha}{\left( {d - \frac{1}{\alpha}} \right)\left( {\alpha^{2} - \alpha_{o}^{2}} \right)}.}} & (13)\end{matrix}$

[0114] Since d is fixed and known $\frac{d\quad i}{i},$

[0115] α, and α_(o) are computed by equations (10) and (5). It isimportant to note that in the final ratio of${F\left( \frac{\Delta \quad H}{H} \right)},$

[0116] the access blood proration value, X_(b), cancels out. Thisremoves vascular access size, volume, or depth dependence from the finalresult. Likewise, the $\frac{d\quad i}{i}$

[0117] and $\frac{\alpha}{\alpha^{2} - \alpha_{o}^{2}}$

[0118] ratios eliminate skin color variations.

[0119] In order to use indicator dilution techniques to measure vascularaccess flow rates during routine hemodialysis, the indicator must beinjected upstream and its concentration detected downstream in the bloodflowing through the vascular access site 14. Reversing the dialysisblood lines 16 a and 16 b during the hemodialysis treatment permitsapplication of indicator dilution by direct injection of the indicatorinto the dialysis venous tubing 16 b. Because the TQ_(a) sensor 12 candetect a dilution signal downstream of the venous needle 24 through theskin, a unique application of indicator dilution principles permitsdetermination of the vascular access flow rate without reversal of thedialysis blood lines 16 a and 16 b. Various methods of measuringvascular access blood flow rate, as well as a method for locatingaccesses and grafts and localizing veins in normal patients, using theTQ_(a) sensor 12 are described in co-pending application entitled“Method of Measuring Transcutaneous Access Blood Flow,” filed on evendate herewith, Attorney Docket P65685US0, which is incorporated hereinin its entirety.

[0120] The accuracy of the measurements taken using the TQ_(a) sensor 12depends critically on at least two factors. As can be seen in equation(3) above, the calculated access flow rate depends directly on thevolume of saline injected; therefore, care must be taken to inject agiven amount of saline over a specified time interval. The latter doesnot need to be known precisely; however, it is important that it be lessthan approximately 10 seconds to avoid significant interference due tocardiopulmonary recirculation (CPR) of the injected saline. The secondfactor that is important to consider in the accuracy of the TQ_(a)measurements is the placement of the TQ_(a) sensor 12 to accuratelydetermine changes in hematocrit through the skin. The sensor 12 must beplaced directly over the vascular access site 14 approximately 25 mmdownstream of the venous needle 24 in the specified orientation toaccurately determine the relative changes in hematocrit. Additionalvariability due to sensor placement does not appear, however, to besignificant, in that small variations in sensor placement do notsignificantly influence the measured vascular access flow rate. Anadditional concern is whether variations in accuracy of measurementstaken using the TQ_(a) sensor 12 may occur with access sites that arenot superficial or if the access diameter is very large; however,varying the spacing of sensor elements eliminates difficultiesassociated with very large accesses or with deeper access sites such asthose typically found in the upper arm or thigh. Less accurate resultswould also be obtained if the sensor 12 does not accurately detectchanges in hematocrit due to significant variation in skin pigmentation.The TQ_(a) sensor in accordance with the invention has been specificallydesigned to account for the individual absorption and scatteringproperties of patient tissues, through the use of 805 nm-880 nm LEDoptical technology, and the normalized nature of the measurements$\left( \frac{di}{i} \right)$

[0121] suggests that the sensitivity of the calculated vascular accessflow rate to skin melanin content is minimal.

[0122] Referring now to FIGS. 2-6, there is shown a first embodiment ofthe TQ_(a) sensor 100 in accordance with the present invention for thetranscutaneous measurement of vascular access blood flow in ahemodialysis shunt or fistula 14. In this embodiment two emitters 102 aand 102 b and two detectors 104 a and 104 b are arranged in alignmentalong an axis A1 on a substrate 110. As mentioned above, this embodimentis employed if a gradient in α_(o) exists in the area of interest (as isoften the case in vivo), as multiple measurements must be made toestablish the nature of the gradient and provide an averaged estimate ofα_(o).

[0123] The sensor 100 has an access placement line L1 perpendicular tothe axis A1. For proper operation, the sensor 100 must be placed withthe access placement line L1 over the venous access site (shunt) 14. Oneof the emitters (the “inboard emitter”) 102 a and one of the detectors(the “inboard detector”) 104 a are placed at inboard positions on eitherside of and equidistant from the access placement line L1. The secondemitter (the “outboard emitter”) 102 b is placed at a position outboardof the inboard detector 104 a, while the second detector (the “outboarddetector”) 104 b is placed at a position outboard of the inboard emitter102 a, so that the emitters 102 a and 102 b and detectors 104 a and 104b alternate. The spacing between the emitters 102 a and 102 b and thedetectors 104 a and 104 b is uniform.

[0124] The substrate 110 is provided with apertures 116 in its lowersurface (the surface which in use faces the access site 20) forreceiving the emitters 102 a and 102 b and the detectors 104 a and 104b. The apertures 116 are sized so that the emitters 102 a and 102 b andthe detectors 104 a and 104 b lie flush with the lower surface of thesubstrate 110.

[0125] Preferably, the upper surface of the substrate 110 is marked withthe access placement line L1. The upper surface of the substrate 110 mayalso be provided with small projections 120 or other markings above theapertures 116 indicating the locations of the emitters 102 a and 102 band the detectors 104 a and 104 b.

[0126] The circuitry (not shown) associated with the emitters 102 a and102 b and the detectors 104 a and 104 b can be provided as a printedcircuit on the lower surface of the substrate 110. The substrate 110 ismade of a material that is flexible enough to conform to the contours ofthe underlying tissue but rigid enough to have body durability.

[0127] As shown in FIG. 7, there are three illuminated volumes or“glowballs” 130 a, 130 b, and 130 c in the tissue, T, seen by the twodetectors 104 a and 104 b: a first glowball 130 a representing thereflective penetration volume (α) of the inboard emitter 102 a throughthe access site tissue as seen by the inboard detector 104 a in theprocess of determination of the access Hematocrit; a second glowball 130b representing the reflective penetration (α_(o1)) of the inboardemitter 102 a through the non-access site tissue that surrounds theaccess site 14 as seen by the outboard detector 104 b; and a thirdglowball 130 c representing the reflective penetration (α_(o2)) of theoutboard emitter 102 b through the non-access site tissue that surroundsthe access site 14 as seen by the inboard detector 104 a. An estimate ofα_(o) is made by averaging α_(o1) and α_(o2). That is, $\begin{matrix}{\alpha_{o} = \frac{\alpha_{o1} + \alpha_{o2}}{2}} & (14)\end{matrix}$

[0128] Due to the depth of the access site 14, in order for thecross-section of the access site 14 to be enclosed by the glowball 130 aof the inboard emitter 102 a seen by the inboard detector 104 a, thespacing between the inboard and outboard detectors 104 a and 104 b istypically 24 mm.

[0129] Referring now to FIGS. 8-12, there is shown a second embodimentof the TQ_(a) sensor 200 in accordance with the present invention. Inthis embodiment two emitters 202 a and 202 b and one detector 204 arearranged in alignment along an axis A2 on a substrate 210. As mentionedabove, this embodiment is employed if the tissue, T, is more or lesshomogenous, and it is only necessary to make a single reference a_(o)measurement.

[0130] The sensor 200 has an access placement line L2 perpendicular tothe axis A2. One of the emitters (the “inboard emitter”) 202 a and thedetector 204 are placed at inboard positions on either side of andequidistant from the access placement line L2. The second emitter (the“outboard emitter”) 202 b is placed at a position outboard of thedetector 204, so that the emitters 202 a and 202 b and the detector 204alternate. The spacing between the emitters 202 a and 202 b and thedetector 204 is uniform.

[0131] The substrate 210 is provided with apertures 216 in its lowersurface for receiving the emitters 202 a and 202 b and the detector 204.The apertures 216 are sized so that the emitters 202 a and 202 b and thedetector 204 lie flush with the lower surface of the substrate 210.

[0132] Preferably, the upper surface of the substrate 210 is marked withthe access placement line L2, and also is marked with “plus” and “minus”signs 218 a and 218 b, which indicate the direction to move the sensor200 left or right. The upper surface of the substrate 210 may also beprovided with small projections 220 or other markings above theapertures 216 indicating the locations of the emitters 202 a and 202 band the detector 204.

[0133] The circuitry (not shown) associated with the emitters 202 a and202 b and the detector 204 can be provided as a printed circuit on thelower surface of the substrate 210. The substrate 210 is made of amaterial that is flexible enough to conform to the contours of theunderlying tissue but rigid enough to have body durability.

[0134] As shown in FIG. 13, there are two illuminated “glowballs” 230 aand 230 b seen by the single detector 204: a first glowball 230 arepresenting the reflective penetration (α) of the inboard emitter 202 athrough the access site tissue as seen by the single detector 204 in theprocess of determination of the access Hematocrit; and a second glowball230 b representing the reflective penetration (α_(o)) of the outboardemitter 202 b through the non-access site tissue that surrounds theaccess site 14 as seen by the single detector 204.

[0135] Referring now to FIGS. 14-18, there is shown a third embodimentof the TQ_(a) sensor 300 in accordance with the present invention. Thethird embodiment is similar to the second embodiment, except that oneemitter 302 and two detector 304 a and 304 b are arranged in alignmentalong an axis A3 on a substrate 310.

[0136] The sensor 300 has an access placement line L3 perpendicular tothe axis A3. The emitter 302 and one of the detectors (the “inboarddetector”) 304 a are placed at inboard positions on either side of andequidistant from the access placement line L3. The second detector (the“outboard detector”) 304 b is placed at a position outboard of theemitter 302, so that the emitter 302 and the detectors 304 a and 304 balternate. The spacing between the emitter 302 and the detectors 304 aand 304 b is uniform.

[0137] The substrate 310 is provided with apertures 316 in its lowersurface for receiving the emitter 302 and the detectors 3204 a and 3204b. The apertures 316 are sized so that the emitter 302 and the detectors304 a and 304 b lie flush with the lower surface of the substrate 210.

[0138] The circuitry (not shown) associated with the emitter 302 and thedetectors 304 a and 304 b can be provided as a printed circuit on thelower surface of the substrate 310. The substrate 310 is made of amaterial that is flexible enough to conform to the contours of theunderlying tissue but rigid enough to have body durability.

[0139] Preferably, the upper surface of the substrate 310 is marked withthe access placement line L3, and also is marked with “plus” and “minus”signs 318 a and 318 b, which indicate the direction to move the sensor300 left or right. The upper surface of the substrate 310 may also beprovided with small projections 320 or other markings above theapertures 316 indicating the locations of the emitter 302 and thedetectors 304 a and 304 b.

[0140] As shown in FIG. 19, there are two illuminated “glowballs” 330 aand 330 b seen by the detectors 304 a and 304 b: a first glowball 330 arepresenting the reflective penetration (a) of the single emitter 302through the access tissue as seen by the inboard detector 304 a in theprocess of determination of the access Hematocrit; and a second glowball330 b representing the reflective penetration (α_(o)) of the singleemitter 302 through the non-access site tissue that surrounds the accesssite 14 as seen by the outboard detector 304 b In the first threeembodiments, the placement of the emitters and detectors permits all ofthe measurements to be made only in tissue volumes perpendicular to theaccess site 14. There will now be discussed fourth and fifthembodiments, in which the placement of the emitters and detectorspermits measurements to be made in tissue areas parallel, as well asperpendicular, to the access site 14.

[0141] Referring to FIGS. 20-22, there is shown a fourth embodiment ofthe TQ_(a) sensor 400 in accordance with the present invention. In thefourth embodiment, a flexible components layer 410 is provided having anaccess placement line L4. An upstream and a downstream emitter 402 a and402 b are arranged on the components layer 410 along a first diagonalline D1 forming a 45° angle with the access placement line L4, and anupstream and a downstream detector 404 a and 404 b are arranged along asecond line D2 perpendicular to the first line at its point ofintersection P with the access placement line L4. The upstream anddownstream emitters 402 a and 402 b and the upstream and downstreamdetectors 404 a and 404 b are equidistant from the point of intersectionP. It will thus be seen that the upstream emitter 402 a and thedownstream detector 404 b lie on one side of the access placement lineL4 along a line parallel thereto, and the upstream detector 404 a andthe downstream emitter 402 b lie on the other side of the accessplacement line LA along a line parallel thereto; and that the upstreamemitter 402 a and the upstream detector 404 a lie along a lineperpendicular to the access placement line L4, as do the downstreamemitter 402 b and the downstream detector 404 b.

[0142] In the TQ_(a) sensor 400 in accordance with the fourthembodiment, the circuitry associated with the emitters 402 a and 402 band the detectors 404 a and 404 b is also incorporated in the flexiblecomponents layer 410. The components layer 410 has a lower surface thatfaces the access site 14, and an upper surface that faces away. Theemitters 402 a and 402 b and the detectors 404 a and 404 b may protrudefrom the lower surface of the components layer 410. A cover layer 412 offlexible foam or the like covers the upper surface of the componentslayer 410. A spacer layer 414 of flexible foam or the like covers thelower surface of the components layer 410, and has apertures 416 inregistration with the emitters 402 a and 402 b and the detectors 404 aand 404 b, so that each emitter and detector is received in its owncorresponding aperture 416. The spacer layer 414 has an upper surfacethat contacts the lower surface of the components layer 410 and a lowersurface that faces away from the components layer 410.

[0143] Preferably, the upper surface of the cover layer 412 is markedwith the access placement line L4, and also is marked to indicate whichend of the access placement line L4 is to be placed adjacent the venousneedle 24, to assist in proper placement. Also, the TQ_(a) sensor 400preferably is elongated in the direction of the access placement lineL4, in order to ensure the proper placement of the emitters 402 a and402 b and the detectors 404 a and 404 b relative to the venous needle24.

[0144] In order to hold the TQ_(a) sensor 400 in place, a transparentadhesive layer 420 can be applied to the lower surface of the spacerlayer 414. The adhesive can be any suitable pressure sensitive adhesive.A release liner 422 covers the adhesive layer 420. Prior to use, therelease layer 424 is removed from the adhesive layer 420 of the TQ_(a)sensor 400, and the TQ_(a) sensor 400 is adhered to the access site 14.

[0145] As shown in FIGS. 23-26, there are four illuminated “glowballs”seen by the upstream and downstream detectors: a first glowball 430 arepresenting the reflective penetration (a) of the upstream emitter 402a through the access site tissue as seen by the upstream detector 404 ain the process of determination of the access hematocrit (FIG. 23); asecond glowball 430 b representing the reflective penetration (a) of thedownstream emitter 402 b through the access site tissue as seen by thedownstream detector 404 b in the process of determination of the accessHematocrit (FIG. 24); a third glowball 430 c representing the reflectivepenetration (α_(o1)) of the upstream emitter 402 a through thenon-access site tissue that surrounds the access site 14 as seen by thedownstream detector 404 b (FIG. 25); and a fourth glowball 430 drepresenting the reflective penetration (α_(o2)) of the downstreamemitter 404 b through the non-access site tissue that surrounds theaccess site 14 as seen by the upstream detector 404 a (FIG. 26). Anestimate of α_(o) is again made by averaging α_(o1) and α_(o2).

[0146] Referring to FIGS. 27-29, there is shown a fifth embodiment ofthe TQ_(a) sensor 500 in accordance with the present invention. In thefifth embodiment, a substrate 510 is provided having an access placementline L5. A first upstream emitter 502 a and a downstream emitter 502 bare arranged on the substrate 510 along a first diagonal line D3 forminga 45° angle with the access placement line L5, and upstream anddownstream detectors 504 a and 504 b are arranged along a second line D4perpendicular to the first line at its point of intersection P with theaccess placement line L4, exactly as in the fourth embodiment, with thefirst upstream and the downstream emitters 502 a and 502 b and theupstream and downstream detectors 504 a and 504 b being equidistant fromthe point of intersection P. In addition, the second, third, fourth,fifth, and sixth upstream detectors 502 c, 502 d, 502 e, 502 f, and 502g are arranged in alignment along a line defined by the first upstreamemitter 502 a and the upstream detector 504 a, with the fourth detector502 e lying on the access placement line L5. The second, third, fourth,fifth, and sixth emitters 502 c, 502 d, 502 e, 502 f, and 502 g areuniformly spaced between the first upstream emitter 502 a and theupstream detector 504 a and can be used to locate the access. Inaddition, pairs of emitters 502 a and 502 c-502 g can be used todetermine the diameter of the access.

[0147] The cover layer 512, spacer layer 514, adhesive layer 522, andrelease liner 524 of the sensor 500 in accordance with the fifthembodiment are identical to those of the sensor 400 of the fourthembodiment, except that the apertures 516 in the spacer layer 514 willbe placed in accordance with the placement of the emitters 502 a-502 gand the detectors 504 a and 504 b in the components layer 510 of thefifth embodiment.

[0148] As shown in FIGS. 30 and 31, there are six illuminated glowballsperpendicular to the access site 14 and one illuminated glowballparallel to the access site 14 that are seen by the upstream detector504 a: a first glowball 530 a representing the reflective penetration(α) of the first upstream emitter 502 a through the access site tissuein the process of determination of the access site Hematocrit (FIG. 30);a second glowball 530 b representing the reflective penetration (α_(o1))of the downstream emitter 502 b through the non-access site tissue thatis parallel to the access site 14 (FIG. 31); a third glowball 530 crepresenting the reflective penetration of the second upstream emitter502 c through both non-access and some of the access volume (FIG. 30); afourth glowball 530 d representing the reflective penetration of thethird upstream emitter 502 d through both non-access and some of theaccess volume (FIG. 30); a fifth glowball 530 e representing thereflective penetration of the fourth upstream emitter 502 e through bothnon-access and some of the access volume (FIG. 30); a sixth glowball 530f representing the reflective penetration of the fifth upstream emitter502 f through non-access the access volume (FIG. 30); and a seventhglowball 530 g representing the reflective penetration of the sixthupstream emitter 502 g through non-access volume (FIG. 30).

[0149] As shown in FIGS. 32 and 33, there are two illuminated“glowballs” seen by the downstream detector 504 b: an eighth glowball530 h representing the reflective-penetration (α_(o2)) of the firstupstream emitter 502 a through the non-access site tissue that isparallel to the access site 14 (FIG. 32); and a second glowball 530 irepresenting the reflective penetration (a) of the downstream emitter502 b through the access site tissue in the process of determination ofthe access Hematocrit (FIG. 33). An estimate of α_(o) is made byaveraging α_(o1) and α_(o2), and then using equation (13) to determine${F\left( \frac{\Delta \quad H}{H} \right)}.$

[0150] Due to the depth of the access site 14, in order for thecross-section of the access site 14 to be enclosed by the glowball ofthe first upstream emitter 502 a seen by the upstream detector 504 a,the spacing between the first upstream emitter 502 a and the upstreamdetector 504 a is typically 24 mm. The remaining upstream emitters 502c-502 g are equally spaced between the first upstream emitter 502 a andthe upstream detector 504 a. Similarly, the spacing between thedownstream emitter 502 b and the downstream detector 504 b are typically24 mm.

[0151] As indicated above, in all of the embodiments, the emitters arepreferably LEDs that emit light at a wavelength of 805 nm-880 nm, andthe detectors are silicon photodiodes. In the first three embodimentsshown in FIGS. 2-6, 8-12, and 14-18, the substrate preferably isprovided with an exterior covering (see FIG. 34) of a plastic material,for example urethane or silicone, and the emitters and detectors lieflush with the lower surface of the exterior covering, that is, thesurface that faces the skin, so that the emitters and detectors lie onthe skin. In the fourth and fifth embodiments shown in FIGS. 20-22 and27-29, each emitter and detector is recessed in an aperture. The fourthand fifth embodiments use more LED's than the other embodiments.

[0152] Also in all of the embodiments, an emitter-detector separation isrequired so that the reflectance of the first layer of tissue (anon-blood layer of epithelium) does not further exaggerate a multiplescattering effect, as discussed in U.S. Pat. No. 5,499,627, which isincorporated herein by reference in its entirety.

[0153] Further, in the all of the embodiments, the distance between eachadjacent pair of emitters and detectors must be sufficient for a portionof the access site 14 to be enclosed within the illuminated volume or“glowball” of the inboard emitter. This distance typically is about 24mm, except as described above with respect to the fifth embodiment.

[0154] Finally, in all of the embodiments, the sensor can be fastened inplace using surgical tape. Alternatively, any of the embodiments can bemade as a disposable adhesive patch that cannot be recalibrated and usedagain. Referring to FIG. 34, a sensor 600 includes a substrate 610 thathouses a plurality of emitters and detectors (not shown) as previouslydescribed, a circuit 652 printed on the skin side of the substrate 610,and an exterior covering 654 covering the circuit 652 and the exposedsides of the substrate 610. The substrate 610 can comprise a flexiblematerial such as MYLAR on which conductive paint has been deposited todefine a circuit. Apertures 656 are formed through the skin side of theexterior covering 654 in registration with circuit junctions that arecovered by conductive paint that allows continuity across the junctions.Plugs 660 are inserted into the apertures 656 in such a fashion thatthey adhere to the conductive paint at the circuit junctions. The skinside of the exterior covering 654 is covered by a removable protectivelayer 662, to which the plugs 660 are also affixed.

[0155] Following removal of the sensor 600 from its sterile package andpre-use test and calibration, the protective surface protective layer662 must be removed in order for the sensor 600 to take a measurement.Because the plugs 660 are adhered to the protective layer 662, when theprotective layer 662 is peeled off, the plugs 660 are pulled out oftheir apertures 656 along with the conductive paint covering the circuitjunctions. The circuitry is designed such that once the circuit isbroken, the sensor 600 cannot be calibrated again, and can only be usedto take one measurement. The sensor 600 thus cannot be re-used.

[0156] Operability of the TQ_(a) sensor in accordance with the inventionwas confirmed in in vivo tests in 59 hemodialysis patients. Prior to thestudy dialysis session, a disposable tubing with an injection port(CO-daptoR, Transonic Systems, Ithaca, N.Y., USA) was placed between thevenous dialysis tubing and the venous needle. The dialysis circuit wasprimed with saline in usual fashion taking extra care to remove any airbubbles from the venous injection port.

[0157] Within the first hour of dialysis, access recirculation was firstmeasured by the HD01 monitor (Transonic Systems). Then, the dialyzerblood pump was stopped, the dialysis lines were reversed from theirnormal configuration, and the access blood flow rate was determined, induplicate, by the HD01 monitor (Transonic Systems). Injection of salinewas performed using the saline release method (abstract: Krivitski etal, J Am Soc Nephrol 8:164A, 1997). The dialyzer blood pump was againstopped and the dialysis lines were returned to their normalconfiguration.

[0158] After the dialysis blood lines were returned to the normalconfiguration and the dialyzer blood pump was restarted, thetranscutaneous hematocrit sensor was placed on the skin over thepatient's vascular access approximately 25 mm downstream of the venousneedle. Thirty ml of normal saline solution were then injected into theinjection port of the disposable tubing adjacent to the venous needle ata rate of approximately 300 nm/min to determine access blood flow rateusing the TQ_(a) sensor of the invention. In six patients, saline wasinjected directly into the arterial dialysis needle before connectingthe needle to the complete dialysis circuit. In two patients, saline wasinjected directly into the access by using a needle and syringe. Thedata from these various methods were combined together, independent ofwhere saline was injected into the access. The resulting$F\left( \frac{\Delta \quad H}{H} \right)$

[0159] signal proportional to $\frac{\Delta \quad H}{H}$

[0160] is shown in FIG. 35 with the saline bolus. In 38 patients, thismeasurement was performed in duplicate to assess the replicability ofthe method.

[0161] All measured and calculated values are reported as mean±SD. Thesignificance of differences in calculated vascular access flow ratesdetermined using the TQ_(a) sensor and those determined by the HD01monitor was determined using a paired Student's t-test. The variabilityof the slope and intercept from the regression equation is expressed as± the estimated SD (or the SE). The results from the replicability andreproducibility studies are expressed as the average coefficient ofvariation for the duplicate measurements. P values less than 0.05 wereconsidered statistically significant.

[0162] The patients studied were predominantly male and Caucasian; 5Black and 1 Native American patients were studied. Although thedistribution of patient race in the study was not representative of thatwithin the United States as a whole, it was representative of thepopulation in the geographical region where the test was conducted. Theage of the patients, the fraction of diabetic patients and the fractionof patients with synthetic PTFE grafts were similar to those for chronichemodialysis patients in the United States. Eleven patients were studiedtwice and one patient was studied three times. All other patients werestudied once for a total of 72 measurements. Access recirculation wassignificant in three patients. In those patients, the blood pump settingwas reduced to 150 ml/min to eliminate access recirculation beforecompleting the study protocol.

[0163]FIG. 36 shows values of the vascular access flow rate determinedusing the TQ_(a) sensor plotted versus that determined by the HD01monitor. The best-fit linear regression line has a slope of essentiallyunity and a small y-intercept. There was no significant differencebetween vascular access flow rates determined using the TQ_(a) sensorand those determined by the HD01 monitor; the mean absolute differencebetween these methods was 71±63 ml/min. When these results were analyzedfor various patient subgroups (male vs. female, black vs. white,diabetic vs. nondiabetic, synthetic grafts vs. native fistulas),excellent agreement between the measured access blood flow rates wassimilarly observed.

[0164] Because the optical TQ_(a) sensor in accordance with theinvention can accurately determine instantaneous changes in hematocrit,it permits use of the bolus injection indicator dilution approach(Henriques-Hamilton-Bergner Principle). This optical approach is likelyto be of considerable interest to nephrologists since it is alsopossible to determine the vascular access flow rate when the patient isin the physician's office or in the clinic and not being treated byhemodialysis by simply injecting saline directly into the access andmeasuring with a downstream TQ_(a) sensor. During the initial study,eight patients had vascular access flow rate determinations by directinjection of saline into the access prior to dialysis; their resultswere later confirmed once the dialysis circuit was in place andfunctioning. Furthermore, two additional studies were perforedexcusively by injecting saline into the access, with excellent results.Thus, it may now be possible to use the TQ_(a) sensor in accordance withthe invention to regularly monitor the vascular access flow rate as anindicator of access function when the patient is not being dialyzed, aswell as during maturation of native fistulas prior to first use.

[0165] Modifications and variations of the above-described embodimentsof the present invention are possible, as appreciated by those skilledin the art in light of the above teachings. For example, the sensor inaccordance with the present invention can be used to measure bloodconstituents other than hematocrit, such as albumen and glucose, inwhich case the LEDs emit different wavelengths suited to the specificconstituent.

[0166] Further, the detector-emitter arrangement of the sensor inaccordance with the present invention, and in particular of the sensor110 shown in FIG. 7, allows for precise access location, as a “flowfinder,” and also can be used to locate grafts and to localize veins innormal patients for more efficient canulatization. In this connection,the sensor 110 is placed directly on the skin over the approximate areaof the access, graft, or vein, and values of α, α₁, and α₂ arecalculated as described above. A reference ratio, RR, is developed,where:${RR} = {\left( {1 - \frac{\alpha_{o1}}{\alpha_{02}}} \right) \times 100}$

[0167] When RR<±15, then the access or graft or vein is “centered”correctly or found between the inboard LED 102 a and the inboarddetector 104 a. Also, a signal strength (SS) indicator advises the userwhether a sufficient signal is present for an accurate measurement,where${SS} = \left\lbrack {\left( {\alpha - \left( \frac{\alpha_{o1} + \alpha_{o2}}{2} \right)} \right\rbrack \times 100} \right.$

[0168] When SS>40, then a sufficient amount of the access or graft orvein is within the illuminated volume of tissue. If RR is not <+15 (thatis, if RR≧2±15), or if SS is not >40 (that is, if SS is <40), then thesensor 110 is moved right or left (+ or −) to find the appropriate spotor location.

[0169] It is therefore to be understood that, within the scope of theappended claims and their equivalents, the invention may be practicedotherwise than as specifically described.

What is claimed is:
 1. A sensor for the transcutaneous measurement ofvascular access blood flow comprising at least one photoemitter and atleast one photodetector, the total number of photoemitters andphotodetectors being at least three, the photoemitters and thephotodetectors being collinear and alternatingly arranged.
 2. A sensorfor the transcutaneous measurement of vascular access blood flowcomprising: a substrate having an axis and an access placement lineperpendicular to the axis; an inboard emitter and an inboard detectorpositioned on the substrate on either side of and spaced the samedistance δ from the access placement line.
 3. The sensor of claim 2,further comprising at least one of an outboard emitter and an outboarddetector spaced a distance δ from the inboard detector and the inboardemitter, respectively.
 4. The sensor of claim 3, wherein all of theemitters and detectors are collinear and are alternatingly arranged. 5.The sensor of claim 4, wherein the inboard emitter is the only emitterand wherein there is an inboard detector and an outboard detector oneither side of the inboard emitter.
 6. The sensor of claim 4, whereinthe inboard detector is the only detector and wherein there is aninboard emitter and an outboard emitter on either side of the inboarddetector.
 7. The sensor of claim 4, wherein there is at least oneoutboard emitter and at least one outboard detector.